Inducible nitric oxide synthase and bcl-2 expression in nasopharyngeal cancer: correlation with outcome of patients after radiotherapy.

PURPOSE: The expression of inducible nitric oxide synthase (iNOS) and bcl-2 proteins was evaluated and the prognostic significance determined in nasopharyngeal cancer (NPC) patients treated by radiotherapy. METHODS AND MATERIALS: Tissue sections from 55 patients with NPC were assessed for iNOS and bcl-2 protein expression by immunohistochemistry, immunoelectron microscopy, and in situ hybridization before treatment. The markers were correlated with apoptosis (detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay) and clinicopathologic parameters. RESULTS: All NPC sections exhibited positive iNOS and bcl-2 immunoreactivity, with a mean percentage of 6.24% +/- 0.58% and 17.09% +/- 2.48%, respectively. A significant positive correlation was observed between iNOS expression and the apoptotic index (p < 0.0001, Pearson's r = 0.8518), and bcl-2 expression correlated inversely with apoptosis (p = 0.0001; Pearson's r = -0.6170). A significant inverse correlation was found between iNOS and bcl-2 immunoreactivity (p < 0.0001, Pearson's r = -0.7144). Bcl-2 but not iNOS expression was associated with the stage of the tumor according to the criteria of the American Joint Committee on Cancer (1997) (p < 0.0001). Patients who had recurrence of the tumor and metastasis after radiotherapy had a lower expression of iNOS (p = 0.014 and p = 0.035, respectively), although overall survival was not significantly different statistically. Higher bcl-2 expression was also associated with local tumor recurrence (p = 0.005) but not with metastasis or overall survival. CONCLUSION: It appears that iNOS and bcl-2 expression may be potentially useful biomarkers for predicting the outcome of radiotherapy in NPC patients.

Glutathione S-transferase pi expression in nasopharyngeal cancer.

BACKGROUND: Glutathione S-transferase pi (GST-pi) is an enzyme that catalyzes the conjugation of electrophilic substrates and prevents oxidative damage. Although GST-pi expression has been analyzed in many cancers, the significance of GST-pi expression in nasopharyngeal cancer (NPC), a tumor with a high treatment failure rate, is still unclear. OBJECTIVE: To elucidate the significance of GST-pi expression in NPC. DESIGN: Evaluation of GST-pi expression in NPC tissue specimens and determination of its relationship with tissue iron (a pro-oxidant) and clinicopathological factors in NPC. MATERIALS AND METHODS: Immunohistochemical expression of GST-pi was carried out in 55 NPC and 4 normal nasopharyngeal tissue sections. Eleven nasopharyngeal biopsy specimens (4 normal and 7 NPC) were analyzed for tissue iron levels. The expression of GST-pi in NPC was correlated with corresponding tissue iron levels. The relationships between GST-pi expression with sex, race, tumor stage, cervical nodal status, and clinical staging were also analyzed. RESULTS: Glutathione S-transferase pi immunoreactivity was observed in all NPC sections, with the percentage of immunopositive cells ranging from 1.0% to 72.0%. Tissue iron levels were significantly higher in the NPC tissues compared with normal tissues (P =.001). A direct correlation was observed between GST-pi expression and total and nuclear iron levels in NPC (P =.01 and P =.047, respectively). A significant association was also observed between GST-pi expression and cervical nodal disease (P =.007). CONCLUSIONS: Nasopharyngeal tumor cells may respond to pro-oxidant conditions by modulating intracellular antioxidant defense. Glutathione S-transferase pi expression appears to be associated with lymphogenous metastasis in NPC.

Role of FNAC in metastasizing malignant mixed tumor of the external auditory canal. A case report.

BACKGROUND: No previous report of metastasizing mixed tumor (pleomorphic adenoma) of the external auditory canal (EAC) has been described. CASE: A 12-year-old, Chinese girl with a history of mixed tumor of the EAC presented with a locally recurrent, aggressive tumor and metastases to the lung and bone five years later. The primary, locally recurrent and metastatic lung tumor showed epithelial and myoepithelial elements with duct formation, chondromyxoid stroma and mitotic activity in the cellular areas on histology. Fine needle aspiration cytology (FNAC) disclosed the presence of spindle cells blending into chondromyxoid fibrillar ground substance in the recurrent and metastatic lung tumors. CONCLUSION: In primary mixed tumor of the EAC, FNAC plays a useful role in the diagnosis of recurrent and metastatic disease. Its ability to identify ominous features, such as increased mitoses in this case, may be limited by sampling. Since cytology and histology cannot reliably prognosticate, long-term follow up of mixed tumor of the EAC after complete excision is advocated.

Vocal fold paralysis following radiotherapy for nasopharyngeal carcinoma: laryngeal electromyography findings.

Laryngeal electromyography was used to study the pattern of neurological injury in three patients with unilateral vocal fold paralysis following radiotherapy for nasopharyngeal carcinoma. The thyroarytenoid and cricothyroid muscles were assessed to give an indication of recurrent and superior laryngeal nerve function. Two patients demonstrated both recurrent and superior laryngeal neuropathy suggesting injury at the skull base. The other patient had only recurrent laryngeal neuropathy indicating more distal involvement. Subclinical neuropathic changes were seen in two cases on the side contralateral to the vocal fold paralysis. These patients may be at increased risk of developing bilateral vocal fold paralysis and potentially life-threatening airway obstruction. Long-term follow-up is recommended for such patients, especially if medialization thyroplasty is being considered. This is the first report describing the use of electromyography to determine the pattern of nerve injury in patients with vocal fold paralysis following head and neck radiotherapy.

Injection laryngoplasty with hyaluronic acid for unilateral vocal cord paralysis. Randomized controlled trial comparing two different particle sizes.

The objective was to determine if particle size affects durability of medialization in patients undergoing injection laryngoplasty (IL) with hyaluronic acid (HA) for unilateral vocal cord paralysis (UVCP). We hypothesized that large particle-size HA (LPHA) persists longer after injection to produce a more durable vocal result. The study design used was a prospective randomized controlled single-blind trial. Patients underwent IL with Restylane (small particle-size HA, SPHA) or Perlane (LPHA) (Q-Med AB, Uppsala, Sweden). Injections were performed transcutaneously in the outpatient clinic. The Voice Handicap Index (VHI) at 6 months postinjection was the primary outcome measure. Secondary outcomes included videostroboscopic findings, and objective acoustic and aerodynamic measures. Seventeen patients (eight SPHA, nine LPHA) were available for follow-up at 6 months. Normalized VHI scores at 6 months after IL were significantly lower in the LPHA group compared to the SPHA group when not adjusted for age and sex (P=0.027). After adjustment, the difference was not significant (P=0.053) but the LPHA group trended toward lower normalized VHI scores. The findings support the hypothesis that the larger particle-size of LPHA makes this material more durable than SPHA for IL. This material may be considered for temporary medialization in patients with UVCP in whom medium-term improvement of at least 6 months is desirable. The transcutaneous route can be used safely in the office setting in non-anticoagulated patients.